Nat Commun 2021 Apr 12;12(1):2185. doi: 10.1038/s41467-021-22479-4.

Therapeutic B-cell depletion reverses progression of Alzheimer’s disease

Ki Kim ^# 1, Xin Wang ^# 1, Emeline Ragonnaud ^# 1, Monica Bodogai ^# 1, Tomer Illouz ^2 3 4, Marisa DeLuca ¹, Ross A McDevitt ⁵, Fedor Gusev ⁶, Eitan Okun ^2 3 4, Evgeny Rogaev ^6 7 8 9, Arya Biragyn ¹⁰

• PMID: 33846335
• PMCID: PMC8042032
• DOI: 10.1038/s41467-021-22479-4

Abstract

The function of B cells in Alzheimer’s disease (AD) is not fully understood. While immunoglobulins that target amyloid beta (Aβ) may interfere with plaque formation and hence progression of the disease, B cells may contribute beyond merely producing immunoglobulins. Here we show that AD is associated with accumulation of activated B cells in circulation, and with infiltration of B cells into the brain parenchyma, resulting in immunoglobulin deposits around Aβ plaques. Using three different murine transgenic models, we provide counterintuitive evidence that the AD progression requires B cells. Despite expression of the AD-fostering transgenes, the loss of B cells alone is sufficient to reduce Aβ plaque burden and disease-associated microglia. It reverses behavioral and memory deficits and restores TGFβ⁺ microglia, respectively. Moreover, therapeutic depletion of B cells at the onset of the disease retards AD progression in mice, suggesting that targeting B cells may also benefit AD patients.